iproniazid

How that came to be is a story in itself, but the basics are that in the 1950s scientists discovered, serendipitously, that a drug called iproniazid seemed to help some people with depression.

The Depressing News About Antidepressants 2010

In the early 1950s, a new drug, a nicotine derivative, called iproniazid had been shown to be effective in treating tuberculosis, and studies to further validate its usefulness were being conducted in Europe.

A Q&A with Morton A Meyers about Happy Accidents: Serendipity in Modern Medical Breakthroughs 2010

Nathan Kline, an American psychiatrist, upon learning about the odd effect, saw the potential, and conducted a clinical trial that quickly established iproniazid as the very first anti-depressant.

A Q&A with Morton A Meyers about Happy Accidents: Serendipity in Modern Medical Breakthroughs 2010

If iproniazid was a monoamine oxidase inhibitor MAOI, and if at least one monoamine—serotonin—had been implicated in mental illness, then it stood to reason that iproniazid worked because it stopped the destruction of serotonin, thus increasing its presence in the brain.

MANUFACTURING DEPRESSION Gary Greenberg 2010

The problems began in April 1958, when Frances Simpson, a fifty-five-year-old San Franciscan, met an untimely demise, which the coroner blamed on liver failure due to iproniazid use.

MANUFACTURING DEPRESSION Gary Greenberg 2010

The bad news, however, was that the new article—“CITY RESTRICTS SALE OF ENERGIZING DRUGS”—was mostly about the forty health-department agents who were at that very moment fanning out across the city to impound supplies of iproniazid.

MANUFACTURING DEPRESSION Gary Greenberg 2010

In the next year, Roche, which had all but abandoned iproniazid as an antitubercular, sold the drug to four hundred thousand presumably happy, or at least less unhappy, customers.

MANUFACTURING DEPRESSION Gary Greenberg 2010

MAOI drugs like iproniazid, on the other hand, countered the reserpine effect and raised levels of norepinephrine.

MANUFACTURING DEPRESSION Gary Greenberg 2010

In 1965, he reviewed all the evidence—the reserpine research, the clinical trials with drugs like imipramine and iproniazid, the studies showing evidence of increased catecholamines in the blood and urine of people taking antidepressants, the discoveries of enzyme and reuptake inhibition—and concluded, “There is good evidence to support the thesis that the antidepressant effects of both the monoamine oxidase inhibitors and the imipramine-like drugs are mediated through the catecholamines.”

MANUFACTURING DEPRESSION Gary Greenberg 2010

Within a few years, reports of jaundice and other liver-related ailments in iproniazid users began to pour in.

MANUFACTURING DEPRESSION Gary Greenberg 2010